On a global basis, recessively inherited childhood neurological diseases take an enormous human toll, especially in relatively poor populations with high consanguinity rates. The candidate, an Associate Professor in Neurosciences with tenure, proposes a multifaceted mentoring and career development plan in patient-oriented research towards expanding research capacity in the field of recessive pediatric brain diseases and contributing to improvements in genetic diagnoses and predictions of outcome. This plan will build on the candidate's established strengths in family ascertainment, genetic mapping, disease gene identification and animal models, and apply it towards recessively inherited conditions in the Middle East, which displays among the highest known rates of consanguinity. This will provide opportunities for junior physician scientists both in the US and abroad to obtain formal training in patient-oriented neurogenetic research. The K24 Award will allow for protected time so that 80% of his professional effort can be devoted towards research and mentoring. This program will include: One-on-one mentoring of patient-oriented researchers across the spectrum of training, including medical students, pediatric residents and pediatric neurology fellows, through several innovative institutional programs including the UGSD K12-funded Clinical Research Training program, and will include training in international health and global neurogenetic disease. It will also include professional development for the candidate to allow for new knowledge and skills to be incorporated into the current research platform, with formal, mentored training in complex genetics and epidemiology and systems biology to allow him to translate clinical findings into advances in knowledge and clinical outcomes. Dr. Gleeson's ongoing patient-oriented research on the genetic basis of pediatric brain diseases will serve as research vehicles. His genetic research focuses on the genetic basis of 1) Joubert syndrome, a recessive condition with absence of the cerebellar vermis; 2) Recessive agenesis of the corpus callosum; 3) Recessive epilepsy syndromes; 4) Recessively inherited neuropsychiatric conditions including autism spectrum disorder. The K24 Award will augment his successful patient-oriented research programs and provide the intellectual environment needed to increase the number of physician-scientists capable of carrying out cutting edge global oriented patient-oriented neurogenetic research.